title: Fetal-specific DNA methylation ratio permits noninvasive prenatal diagnosis of trisomy 21.
abstract: The trials performed worldwide toward noninvasive prenatal diagnosis (NIPD) of Down's syndrome (or trisomy 21) have shown the commercial and medical potential of NIPD compared to the currently used invasive prenatal diagnostic procedures. Extensive investigation of methylation differences between the mother and the fetus has led to the identification of differentially methylated regions (DMRs). In this study, we present a strategy using the methylated DNA immunoprecipitation (MeDiP) methodology in combination with real-time quantitative PCR (qPCR) to achieve fetal chromosome dosage assessment, which can be performed noninvasively through the analysis of fetal-specific DMRs. We achieved noninvasive prenatal detection of trisomy 21 by determining the methylation ratio of normal and trisomy 21 cases for each tested fetal-specific DMR present in maternal peripheral blood, followed by further statistical analysis. The application of this fetal-specific methylation ratio approach provided correct diagnosis of 14 trisomy 21 and 26 normal cases.
authors.affiliation: Cytogenetics and Genomics Department, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: Elisavet A
authors.initials: EA
authors.lastname: Papageorgiou
authors.forename: Alex
authors.initials: A
authors.lastname: Karagrigoriou
authors.forename: Evdokia
authors.initials: E
authors.lastname: Tsaliki
authors.forename: Voula
authors.initials: V
authors.lastname: Velissariou
authors.forename: Nigel P
authors.initials: NP
authors.lastname: Carter
authors.forename: Philippos C
authors.initials: PC
authors.lastname: Patsalis
mesh_terms: D001483:Base Sequence; D016022:Case-Control Studies; D004247:DNA / Q000097:blood / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D016002:Discriminant Analysis; D004314:Down Syndrome / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D005333:Fetus / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods; D011237:Predictive Value of Tests; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D012016:Reference Values
chemical_list: D017931:DNA Primers; D004247:DNA